N-substituted pyrroles and process



formed at high temperatures. is generally preferred.

United States Patent N-SUBSTITUTED PYRROLES AND PROCESS Newman M.Bortnick, Oreland, and Marian F. Fegiey, Mont Clare, Pa., assignors toRohm & Haas Company, Philadelphia, Pa., a corporation of Delaware NoDrawing. Application August 26, 1953, Serial No. 376,742

9 Claims. (Cl..260-309.7)

This invention I deals with a process for preparing pyrroles having anN-substituent by reacting a primary amine and abis(tert-amino)-1,3-butadiene. This invention also deals withN-substituted pyrroles which now become readily available for the firsttime.

Interest in pyrrole has been great since it is an essential unit in suchimportant substances as chlorophyll and hemoglobin. Yet lack of a goodsynthesis for substituted pyrroles has prevented extended study in thisfield. The present invention provides a good general method for making agreat variety of pyrroles. Since these are highly reactive .substances,they are valuable blocks for reaching a large number of novel compounds.The substituted pyrroles are also useful in the pharmaceutical field,pro viding hypnotics, analgesics, local anesthetics, bactericides,fungicides, and the like.

According to this invention bis(tert-amino)-1,3-butadienes are reactedwith primary amines having ionization constants of at least 4.6)(- andpreferably of 10" or more. The reaction is effected in the presence ofhydrogen ions. amines from the carbon dioxide of the air. With morebasic amines more strongly acidic substances are apparently necessary.It may, therefore, be correctly said that the reaction is effected inthe presence of an acidic catalyst.

As catalysts, there may be used the greatest variety of substances whichprovide hydrogen ions from organic acids through acidic salts to stronginorganic acids. Usually -it is best to work with an acid at least asstrong as propionic or acetic acid. There may be used formic,

phosphoric, polyphosphoric, arylsulfonic, such as p-toluenesulfonic,alkanesulfonic, sulfuric, hydrobromic, hydrochloric, or other acids ofcomparable strength. A particularly convenient catalyst is a mixture ofpropionic or acetic acid and hydrochloric acid. Another useful group ofcatalysts comprises complexes of boron trifluoride and oxygenatedcompounds, such as the coordination complexes of boron trifluoride withethyl ether-or butyl ether, or with a carboxylic acid, such asBF3-2CH3COOH, or with carboxylic esters, such as BFs-ZCHaCOOCzHs, orwith ketones, such as BFs-CHsCOCHs, or withlalcohols, such asBF3-2C4H9OH. Alsoeffective are acid salts and Friedel-Crafts catalystssuch as aluminum chloride, zinc chloride, ferric chloride, and the like.

With the relatively more acidic catalysts the reaction runs atrelatively lower temperatures. Thus, with hydrochloric or 'hydrobromicacid as catalyst, reaction with many amines is promoted at to 30 C.Higher temperatures may, however, be *used and are sometimesadvantageous, particularly to help in the separation of amines. In manycases reaction begins even below 20 C. and in some cases temperaturesmay be carried up to 150 C. or more, although by-products maybe also Arange of 20 to 100 C.

These can be supplied with the less basic lectedbis(tert-amino)-1,3-butadiene.

The reaction may be effected by mixing the two reactants directly andusually adding an acidic catalyst.

Excess amine may serve as solvent or an inert organic wherein R and Rrepresent individually aliphatic hydrocarbon groups of not over fourcarbon atoms each or the benzyl, group and when taken together,saturated divalent aliphatic chains which together with the aminonitrogen form a heterocycle, such as is found in pyrrolidine,piperidine, methylpiperidine, morpholine, thiamorpholine,dimethylmorpholine, or N-methylpiperazine, R and R represent the samegroups and chains, but need not be identical with R and R and R and Rare hydrogen, alkyl groups of .not over eight carbon atoms, or phenylgroups. Other groups which may appear as R and R are alkenyl,cycloalkyl, and substituted groups derived from substituted aldehydes.It is preferred that R and R together and likewise R and R together havea group weight of not over 120.

While any of these bis(tert-amino )-l,3-butadienes can be used asreactants, the most economical starting ma terials are1,4-bis(dime'thylamino)-1,3-butadiene and1,4-bis(diethylamino)-1,3-butadiene. These are available through thethermal isomerization of 1,4-bis(dimethylamino) 2 butyne or -1,4.-bisQdiethylamino) 2 butyne. These and other bis(tert-amino 1,3butadienes are available through the isomerization of corresponding butynes under the influence of lithium, sodium, or sodium hydrocarbons ascatalysts at temperatures preferably from 20 to C. This novel process isdescribed in detail in our application Serial No. 316,558., filedOctober .23, 1952. There may thus be prepared 1,4 bis(dimethylamino) 1,4dioctyl 1,3 butadiene, 1,4 bis(dibutylamino)-1,3-butadiene,1,4-bis(dipropylarnino) -1,3-butadiene, 1,4-bis.(diethylamino) 1(2,4,4-trimethylpentyl)- 1,3-butadiene,1,4-bis(dimethylamino)-1-pheny1-1,3-butadiene,1,4-bis(dimethylamino)-1-isopropyl-1,3 butadiene, 1,4 bis(dimethylamino)1,4 diisopropyl 1,3 butadiene, 1,4 bis(dimethylamino) 1 methyl 1,3butadiene, 1,4 bismorpholino 1,3 butadiene, 1,4 bispyrrolidino 1,3butadiene, 1,4 bispiperidino 1,3 butadiene, 1,4 bis(3,5dimethylmorpholino) 1,3 butadiene, 1,4 bis(N-methylpiperazino) 1,3butadiene, 1,4 bismorpholino 1,4 diphenyl 1,3 butadiene, 1,4-bismorpholino 1,4 diisopropyl 1,3 butadiene, 1,4- bismorpholino l -octyl1,3 butadiene, l morpholino- 4 dim'ethylamino 1,3 butadiene, 1morpholino 1- methyl 4 dimethylamino 1,3 butadiene, 1,4 dithiamorp'holino-1,3-butadiene, etc.

As primary amines, there may be used any primary amine having a fairdegree of bas-icity. Aniline is about as weakly basic an amine as can beused and gives only a very modest yield of the desired 'N-phenylpyrrole.As basicity increases, ease of reaction to pyrroles seems to increase ingeneral, although conversions and yieldsdepend upon the particular amineas well as upon the se- For example, withl,4-bis(dimethylamino)-1,3-butadiene as the selected reactant and underarbitrarily fixed conditions of temperature, time, and catalyst,conversions to N-substituted pyrroles were obtained as follows: withn-butylamine, 64%; with tert-butylamine, 16%; with tert-octylarnine,66%; with 3,5,5-trimethylhexylamine, 67%; with noctadecyl amine, 47%;with allylamine, 67%; with cyclohexylamine, 70%; with hydroxyethylamine,38%; with l-(fi-arninoethyl)-2-imidazolidone, 50%; with benzylamine,43%; with 1-(3-aminopropyl)-2-hexahydropyrimidone, 36%; and so on. It isclear from the large number of amines which have been examined that theprimary amine may be an alkylamine from methyl to octadecyl or analkenyl from allyl through oleyl, an alicyclic amine, such ascyclohexylamine, methylcyclohexylarnine, cyclopentylamine,methylcyclopentylamine, an aralkylamine, such as benzylamine,methylbenzylamine, butylbenzylamine, aniline, or amines of polycycliccompounds such as -amino-3a,4,5,6,7,7a hexahydro-4,7-methanoindene and2-amino-1,7,7-trimethyl-bicyclo( 2,2,1 )-heptane (isobornylamine). Theamines thus far may be summarized by the simple formula RNH2, where R isa hydrocarbon group, whether aliphatic, cycloaliphatic, arylaliphatic,or aryl, provided the amine is at least as basic as aniline.

It will be evident from the above general considerations that R is not,however, confined to hydrocarbon groups. The simple amines may besubstituted with any type of group which does not bring the amine belowthe required level of basicity. Thus, there may be usedhydroxyethylamine, Z-hydroxypropylamine, 3-hydroxypropylamine, thevarious hydroxybutylamines, and so on; ethoxyethylamine,butoxyethylamine, octoxyethylamine, methoxypropylarnine,butoxypropylamine, decyloxypropylamine, hexadecoxypropylarnine,ethoxyethoxypropylamine, octoxyethoxypropylamine, dodecoxy(polyethoxy)-propylamine, phenoxypropylamine, butylphenoxypropylamine,benzyloxypropylamine, dimethylaminoethylamine, dimethylaminopropylamine,diethylaminopropylamine, dibutylaminopropylamine, morpholinopropylamine,pyrrolidinopropylamine, piperidinopropylamine, 3 (N-methylpiperazino)prop-ylamine, vinyloxyethylamine, vinyloxybutylamines,hydroxyethylaminoethylamine, hydroxypropylaminoethylamine,hydroxypropylaminopropylamine, ethylenediamine, 1,2-propanediarnine,1,3-propanediamine, 1,4-butanediamine, 1,6-hexanediamine,diethylenetriamine, triethylenetetramine, etc.

The poly primary amines can be reacted step-wise so that, for example, aZ-aminoethylamino group can be introduced from ethylenediamine, or anethane bispyrrole can be formed. On the other hand with polyaminescontaining one or more secondary or tertiary amino groups along with oneor more primary amino groups only the primary amino groups react andthus basic substituents can be introduced into pyrroles.

The amines of the structure A=N(CH2)XNH2, where X is 2 or 3 and Arepresents two alkyl groups or a divalent chain, are of considerableinterest as they lead to pyrroles having N-aminoalkyl groups which arebasic and which give pharmaceutically important products. When A is aheterocycle-forming group, as the CH2CH2OCH2CH2- of morpholine or the-(CH2)4-5-of pyrrolidine or piperidine, the products are new and ofparticular therapeutic value. A, as noted, may be two alkyl groups, suchas dimethyl, diethyl, or dibutyl. These starting materials alsointroduce basic tertiary nitrogen into the new pyrroles. The tertiaryamine groups are convertible to quaternary ammonium groups by reactionwith a-lkylating agents or the like, such as benzyl chloride ordodecylbenzyl chloride or bromide.

When N-aminoalkyl hexahydropyrimidones or imidazolidones are used, theresulting N-substituted pyrroles are of interest not only in thepharmaceutical field but also in the resin field, for the =NH group ofthe reaction product provides a point at which a methylol group can beintroduced to tie the modified pyrrole into the resin. The above primaryamines may be summarized by the formula wherein A is an alkylene groupof two to three carbon atoms. Thus, A may be ethylene,1,2-propylene, ortrimethylene.

As has been shown a bis(tert-amino)-l,3-butadiene and a primary amineare mixed. A small amount of an acidic catalyst is added. This reactionmixture is stirred and usually heated. If the amine groups from thebutadiene provide volatile amines, they may be taken otf under normal orreduced pressure. Absorption of amine permits an estimate of theprogress of the reaction. When the reaction appears fairly complete orthe reaction becomes slow, the acidic catalyst is destroyed, as byaddition of an alkaline reagent, such as sodium or potassium hydroxideor carbonate. The N-substituted pyrrole formed may then be isolated.Usually the pyrrole is distillable. It may also be isolated byprecipitating it by adding water to the reaction mixture in some casesor an aqueous dilute acid, in which the pyrrole is insoluble. Yields maybe somewhat reduced by this method as some of the :pyrroles aresensitive to acid, especially at elevated temperatures.

Further details of typical preparations of N-substituted pyrroles aregiven in the illustrative examples, in which parts are by weight.

Example 1 There were charged to a reaction vessel equipped with stirrer,thermometer, gas inlet, and gas outlet which was connected to a scrubbercontaining dilute hydrochloric acid, 75 parts of cyclohcxylamine, 75parts of 1,4-b'is- (dimethylamino)-1,3-butadiene, 0.3 part of glacialacetic acid and 0.1 part of concentrated hydrochloric acid. The chargewas stirred, blanketed with nitrogen, and heated at 65 75 C. for fourhours. At this time the amount of dimethylamine absorbed in the scrubberwas about 94% of theoretical. The reaction mixture was treated withpotassium, carbonate and subjected to fractional distillation. The mainproduct fraction was taken at 6263 C./1 mm. The total conversion wasover 70% to NcycloheXyl pyrrole. The product contained by analysis 9.4%of nitrogen (theory 9.38%).

Repetition of this procedure with use of phosphoric acid leads to thesame end products.

Example 2 There were charged to the reaction vessel 75 parts ofn-butylamine, 46 parts of 1,4-bis(dimethylamino)-1,3- butadiene, 0.25part of acetic acid and 0.15 part of hydrochlonic acid. Nitrogen waspassed through the stirred mixture, which was heated at 45 to 90 C. forfour hours, by which time the theoretical amount of dimethylamine hadbeen absorbed in the scrubber. The product was distilled as a mainfraction at 67 C./ 15 mm. in an amount of 26 parts. It had a refractiveindex, N of 1.4729 and contained 11.2% of nitrogen, corresponding incomposition to N-butyl pyrrole, for which the theoretical nitrogencontent is 11.37%.

Example 3 The reaction vessel was charged with 219 parts of aqueousmethylamine, parts of 1,4-bis(dimethylamino)- 1,3-butadiene, 0.5 partof. glacial acetic acid, and 0.3 part of concentrated hydrochloric acid.The mixture was slowly heated to 44 C. In a short time the mixturebecame homogeneous. After about an hour at 44 C. the reaction mixturewas set aside for 16 hours. It was then chilled in an ice bath andacidified with aqueous 18% hydrochloric acid. An oil separated. Theaqueous layer was removed and extracted with ether. The combined oil andether extracts were dried over potassium carbonate and distilled to givea main fraction coming over at 114 C. It had a refractive index, ND23'5,of 1.4855 and corresponded in composition to N-methyl pyrrole. Theconversion was over 46%.

Example 4 There were mixed 72 parts of tert-butylamine, 70 parts of1,4-bis(dimethylamino)-1,3-butadiene, and 0.1 part of hydrochloric acid.The mixture was stirred at about 30 C. for six hours and heated at 45 C.for 3.5 hours. The reaction was treated with an excess of solidpotassium hydroxide and fractionally distilled. The main fraction wastaken at 74-79 C./42 mm. It had a refractive index, NDZO, of 1.4722 andcontained by analysis 10.9% of nitrogen. It was N-tert-butyl pyrrole.

Example 5 There were mixed 30 parts of tert-octylamine,

(CH3 3CCH2C CH3 2NH2 parts of 1,4-b.is(dimethylamino)-1,3-butadiene, 0.1part of hydrochloric acid, and 0.2 part of acetic acid. This mixture wasstirred and heated to about 50 C. for three hours and to 90 C. for ahalf hour. The reaction mixture was washed with, four parts of anaqueous potassium hydroxide solution and distilled. The main fractionwas collected at 45-53 C./0.55 mm; It amounted to l2 parts, a conversionof 66%. On redistillation this product boiled sharply at 58-59 C./1.5mm. It had a refractive index, N13 of 1.4791 and contained 7.8% ofnitrogen (theory 7.81%), corresponding in. composition to N-tert-octylpyrrole.

Repetition of the above procedure with use of sulfuric acid as catalystgave the same endproduct; Likewise, substitution of1,4-bis(diethylaminoy1,3-butadiene or1,4-bis(dibntylamino)-1,3-buta-diene leads to the identical product.

Example 6 There were mixed 31 parts of a branch-chained nonylamine (thenonyl group being obtained from propylene trimer), 14 parts of1,4-bis(dimethy1amino)-1,3butadiene, 0.15 part of acetic acid, and 0.15part of hydrochloric acid. The mixture was heated in an oil bath forthree hours at 5070 C. and at 8090 C. for an hour. Four tenths part ofpotassium hydroxide was added. The mixture was distilled. The fractioncontaining the desired product, N'nonyl pyrrole, was collected at 5262C./0.5 mm. and amounted to 16 parts, This material contained 7.4% ofnitrogen (theory 7.24%). The main fraction was redistilled at 93 94C./4.3 mm. to give a pure product having a refractive index, No, of1.4686. T he conversion was 67%.

Repetition of this procedure with use ofl,4-bis(m=o-rpholino)-1,3-butadiene likewise gives N-nonyl pyrrole.

Example 7 There were mixed 56 parts of n-octadecylamine, 16 parts of1,4-bis(dimethylamino)-l,3-butadiene, 0.1 part of hydrochloric acid, and0.2 part of propionic acid. The mixture was stirred and heated to 60-80C. for three hours. The reaction mixture was filtered and the filtratewa distilled. The main fraction was collected at 178- 132 C./ 1 mm. togive 17 parts of N-n-octadecyl pyrrole. it contained by analysis 4.5% ofnitrogen (theory 4.4%). This product is a waxy solid at roomtemperature. The conversion was 47%.

Example 8 There were mixed parts of allylamine, parts of1,4-bis(dimethylanrino)-1,3butadiene, 0.1 part of hydro chloric acid,and 0.3 part of acetic acid. The mixture was for four hours. Thetheoretical amount of dirnethylamine 6' had been collectedin thescrubber at that time; Addition was made of 0.5 part of sodiumcarbonate. The mixture was distilled, 18 parts of N-allyl pyrrole beingobtained at 61-63 C./ 36 mm. This fraction contained by analysis 12.9%of nitrogen (theory 13.07%). It had a refractive index, No, of 1.4933.

Other alkenylamines may be used in the place of allylamine. In each casethe corresponding N-alkenyl pyrrole is formed.

Example 9 There were mixed 31 parts of ethanolamine, 42 parts of1,4-bis(dimethylamino)-1,3-butadiene, 0.1 part of hydrochloric acid and0.3 part of acetic acid. The mixture was stirred and slowly heated to 65C. where it was held for four hours. About 0.5 part of sodium hydroxidewas added. The reaction mixture was distilled, the main fraction beingcollected at 48-60 C./1 mm. in an amount of 25 parts (a 76% conversion).This was redistilled at 210215 C./760 mm. It contained by analysis12.65% of nitrogen and had a hydroxyl number of 518 compared withtheoretical values of 12.6% and 5 05 respectively, thus corresponding incomposition to bl-fl-hydroxyethyl pyrrole. It had a refractive index of1.5166 at 19 C.

Example 10 There were mixed parts of N(fl -hydroxyethyl)-ethylenediamine, 74 parts of 1,4-bis(dirnethylamino)-1,3- butadiene, 0.2part of hydrochloric acid, and 0.4 part of acetic acid. The mixture wasstirred and heated at 50 C. for 14 hours. There was added about one partof potassium carbonate. The mixture was distilled, the main fractionbeing collected at 109-113 C./65 mm. It correspondedin composition toN-(fi-hydroxyethylaminoethyl pyrrole, containing by analysis 18.4% ofnitrogen (theory 18.2%) and having a refractive index, No, of 1.5218.This preparation is illustrative of the reaction ofhydroxyalkylaminoalkylamines with the bisan'iinobutadienes. It canbesimilarly accomplished with N-(Z-hydroxypropyU- ethyl enediamine, N-Z-hydroxypropyl -propylenediamine, N- Z-hydroxyethyl)trimethylenediamine, N- 2-hydroxypropyl)trimethylenediamine, and so on.

Example 1] There were mixed 50 parts of ,B-aminoethyl vinyl ether, 34parts of 1,4-bis(dimethylamino)-l,3-butadiene, 0.1 part of hydrochloricacid, and 0.3 part of acetic acid. This mixture was stirred and heatedat .55-65 C. for 4.5 hours. it was then Washed with water, dried overanhydrous potassium carbonate, and fraotionally distilled. The mainfraction was collected at 45 52 C./0.7 mm. It contained by analysis 10.4% of nitrogen and corresponded in composition to N-({ivinoxyethyDpyrrole, the theoretical nitrogen content of which is 10.2%.It was redistilled at 100 C. at 20.5 mm; and had a refractive index,NDZO, of 1.5000. The yield was 48%.

This compound is one of particular interest because it can enter intocopclymers and can form polymeric material under the influence of azofree radical catalysts. In place of [i-aminoethy-l vinyl ether there maybe used other aminoalkyl vinyl ethers, such as Z-aminoisobutyl vinylether, Z-aminopropyl vinyl ether, or 3-aminopropyl vinyl ether. Thus theaminoalkyl group may desirably have two to four carbon atoms. ln'eachcase the product is an N-(vinoxyalkyDpyrrole.

Example 12 There were mixed as above 47 parts of a3--morpholinopropylamrine, 60 parts of 1,4-bis(dimethylamino)-1,3-butadiene, 0.1 part of hydrochloric acid, and 0.2 part of acetic acid.The mixture was stirred and heated at 50-55 C. for seven hours. About0.5 part of solid potassium hydroxide was added. The mixture was.distilled, the main fraction being obtained at '-100 C./1 mm. Thisproduct corresponds in composition to N 3-morpholinopropyl) pyrrole.

Morpholinopropylamine may be replaced with the analogous amines of theformula A N(CH2)XNH2 with the reaction yielding analogous N-substitutedpyrroles. Thus, pyrrolidinopropylamine yields N-(3-pyrrolidinopropyl)pyrrole, distilling at 68 C./0.5-2 mm., while piperidinopropylamineyields N-(3-piperidinopropylpyrrole, distilling at 83 C./0.52 mm,

In the same way there may be reacted morpholinoethylamine,pyrrolidinoethylamine, or piperidinoethylamine to give the ethylhomologues of the above compounds. These are very similar in theirproperties to the propyl homologues. There may likewise be made thebutyl derivatives where X in the above formula has a value of four.

Example 13 There were mixed 30 parts of N-fl-aminoethyl-2-imidazolidone, 20 parts of 1,4-bis(dimethylamino)-1,3- butadiene, 0.1part of hydrobromic acid, and 0.3 part of acetic acid. The mixture wasstirred and heated at 60 C. for 0.5 hour, washed with water, and saltedout with potassium carbonate. The reaction product was distilled at174175 C./1.4 mm. in an amount of 9.5 parts of N-irnidazolidonylethylpyrrole. This was redistilled at 195198 C./4 mm. and then crystallizedfrom petroleum ether. The solid product melted at ll4115.5 C. Itcontained by analysis 23.52% of nitrogen (theory 23.45%). This compoundis an autonomic stimulant.

Example 14 There were mixed 54 parts of l-(3-a-minopropyl)2-hexahydropyrimidone, 37 parts of 1,4-bis(dirnethylamino)-1,3-butadiene,0.3 part of hydrochloric acid, and 0.5 part of. acetic acid. The mixturewas stirred and heated at 50 C. for three hours. It was washed with 20parts of water, dried over potassium carbonate, and distilled. The mainfraction was collected at 230-236 C./0.5 mm. It corresponded incomposition to N-hexahydropyrimidonylpropyl pyrrole. This compound isalso useful in the pharmaceutical field, acting on the autonomic nervoussystem.

Example 15 There were mixed 14 parts of 1,4-bis(dimethylamino)-1,3-butadiene, and 9.3 parts of aniline, and 0.1 part of acetic acid.This mixture became solid. It was found that this material was a 1:1adduct of the two materials, corresponding in composition tol-phenyl-2,5-bis(dimethylamino) pyrrolidine. This adduct was distilled.Dimethylamine was evolved, also some aniline. A fraction was obtained at220225 C. which was N-phenyl pyrrole.

There were also mixed 48 parts of aniline, 30 parts of1,4-bis(dimethylamino)-1,3butadiene, 0.1 part of hydrochloric acid, and0.2 part of acetic acid. This mixture was stirred and heated at 55 C.for four hours, Potassium carbonate was added and the reaction mixturewas distilled. At 82-84 C./ 3 mm. a fraction was obtained which waschiefly N-phenyl pyrrole. This fraction was redistilled. The distillatenow became solid, melting 5859 C. This product corresponded incomposition to pure N-phenyl pyrrole.

Example 16 There were mixed 107 parts of benzylamine, 84 parts of1,4-bis(dimethylamino)-1,3-butadiene, 0.2 part of hydrochloric acid, and0.3 part of acetic acid. The mixture was stirred and heated at 70 C. fortwo hours. The product was distilled at 67-68 C./ 0.35 mm, It had arefractive index, NDM, of 1.5655. It corresponded in composition toN-bcnzyl pyrrole.

Example 17 There were mixed 33 parts of ethylenediamine monohydrate, 58parts of 1,4-bis(dimethylamino)-1,3-butadiene, 0.2 part of hydrochloric,and 0.35 part of acetic acid. The mixture was stirred at 50-60 C. for3.5

hours. The mixture was filtered to separate the solid which had formed.This solid was recrystallized from ethyl ether. It melted at 107 C.10SC. and contained by analysis 17.43% of nitrogen, corresponding incomposition to 1,2-dipyrrylethane, which theoretically contains 17.49%of nitrogen. Additional product was obtained by adding 70 parts of waterto the filtrate.

Example 18 There were mixed 39 parts of ethylenediamine, 70 parts of1,4-bis(dimethylamino)-1,3-butadiene, 0.1 part of hydrochloric acid, and0.2 part of acetic acid. The mixture was stirred and heated at 60 C. forfour hours. The reaction mixture was cooled and filtered. The solidproduct was recrystallized from ethyl ether, melting at ]07l08 C. It wasidentified as 1,2-dipyrrylethane. The filtrate was distilled to give afraction boiling at 5053 C./1 mm. This corresponded in composition toN-(Z-aminoethyl) pyrrole It contained by analysis 24.8% of nitrogen(theory 25.4%).

It is thus possible to prepare monoand (ii-substitution products ofalkylenediamines. The diamines may contain two or more carbon atoms inthe alkylene chain. Thus there may be used 1,2-diaminopropane,1,3-diaminopropane, the various diarninobutanes, diaminohexanes,diaminooctanes, or diaminodecanes, and the like.

Example 19 The reaction vessel was charged with 47 parts ofhexamethylenediamine, 50 parts of 1,4-bis-(dimethylamino)-1,3-butadiene, 0.1 part of hydrochloric acid, and 0.25 part of aceticacid. This mixture was heated at C. for 1.7 hours. After addition of 0.3part of potassium carbonate the material was fractionally distilled togive a cut which came over at 91l20 C./l.3 mm, This was found to contain16.87% nitrogen and corresponds to N-(-aminohexyl) pyrrole. Thetheoretical nitrogen content of this material is 16.85%. The product hasa refractive index, No, of 1.4920.

Example 20 A mixture of 30 parts of benzylamine, 16 parts of 1,4-dimorpholino-1,3-butadiene, 0.1 part of hydrochloric acid and 0.2 partof acetic acid was stirred and heated at 65 C. for 1.5 hours. Thereaction mixture was treated with 50 parts of water and acidified withhydrochloric acid whereupon two layers formed. The organic layer wasseparated, dried over anhydrous potassium carbonate, and fractionallydistilled. The main fraction distilled at 7l-73 C./1 mm. This was againWashed with dilute hydrochloric acid to remove the remaining traces offree amine, dried over anhydrous potassium carbonate and distilled togive a fraction boiling at 77 C./0.6 mm. which corresponds incomposition to N-benzylpyrrole.

Example 2] A stirred mixture of 10 parts of1,4-di(2,4,4-trimethylpentyl)-1,4-bis(dimethylamino)-1,3-hutadiene, 4-parts of n-butyl amine, 0.02 part of hydrochloric acid and 0.04 part ofacetic acid was maintained at 5060 C. for three hours. The resultingreaction mixture was washed with dilute hydrochloric acid. Layers wereallowed to separate. The organic layer was taken off and dried onpotassium carbonate. It was then fraetionally distilled; the fractiontaken at 156 C./0.1 mm. was identified as1-butyl-2,5-bis(2,4,4-trirnethylpentyl) pyrrole. The fraction asobtained contained by analysis 4.39% of nitrogen (theory 4.039%).

Example 22 There were mixed 14.5 parts of 1,4-diphenyl-1,4-bis-(dimethylamino)-1,3-butadiene and 10 parts of benzy-lamine. To thismixture there were added 0.2 part of acetic acid and 1.5 parts ofconcentrated hydrochloric acid. The resulting mixture was stirred at6070 C.

for 1.5 hours. It was then treated with potassium carbonate. Ether wasadded to the reaction mixture and the ether solution was filtered. Fromthis solution there was obtained a solid product. This wasrecrystallized from a mixture of dioxane and pentane. The recrystallizedsolid melted at 14-4-144.5 C. Upon analysis, it was found to contain89.15% of carbon, 6.16% of hydrogen, and 5.46% of nitrogen, thuscorresponding to 1- benzyl-2,5-diphenyl pyrrole for which thetheoretical analyses are carbon, 89.28% hydrogen, 6.19%; and nitrogen,5.43%.

In the same way l,4-diphenyl-l,4-bis(dirnethylamino)- 1,3-butadienereacts with n-butylamine to form 1-butyl- 2,5-diphenyl pyrrole, while1-octyl-1,4-bis(dimethylamino)l,3-butadiene yields 1-butyl-2octy1pyrrole and 1 a phenyl 4-isopropyl-l,4-bis(dimethylamino)-1,3-butadieneyields 1-butyl-2-isopropyl-5-phenyl pyrrole. The method of thisinvention thus provides pyrroles having substituents, particularlyhydrocarbon substituents such as methyl, propyl, cctyl, undecyl,l-propenyl, isopropenyl, phenyl, substituted phenyl, cycloheXyl, etc.,in the Z-and/or -positions.

We claim:

1. A process for preparing N-substituted pyrroles which comprisesreacting together between about 20 and 150 C. in liquid phase under theinfluence of an acidic catalyst giving in water at least the acidity ofpropionic acid a primary amine having an ionization constant of at least4.6 and a bis(tert-amino)-1,3-butadiene of the structure wherein R and Rrepresent members of the class consisting of aliphatic hydrocarbongroups of not over four carbon atoms each and the benzyl group whentaken individually and when taken together saturated divalent aliphaticchains which together with the nitrogen atom form a fiveto six-sidedheterocycle, R and R represent members of the class consisting ofaliphatic hydrocarbon groups of not over four carbon atoms each and thebenzyl group when taken individually and when taken together saturateddivalent aliphatic hydrocarbon chains which together with the nitrogenatom form a fiveto six-sided heterocycle, and R and R are members of theclass consisting of hydrogen, alkyl groups of not over eight carbonatoms, and phenyl groups.

2. A process for preparing N-substituted pyrroles which comprisesreacting together between about 20 and 150 C. in liquid phase under theinfluence of an acidic catalyst giving in water at least the acidity ofpropionic acid a primary amine having an ionization con stant of atleast 4.6 10- and 1,4-bis(dimethylamino)- 1,3-butadiene.

3. A process for preparing N-alkyl pyrroles which comprises reactingunder the influence of an acidic catalyst in liquid phase between 20 and100 C. an alkylamine and 1,4-bis(dimethylamino)-1,3-butadiene, saidcatalyst giving in water at least the acidity of propionic acid.

4. A process for preparing N-substituted pyrroles which comprisesreacting together under the influence of an acidic catalyst in liquidphase between 20 and 100 C.

1 0 1,4-bis(dimethylamino)-1,3-butadiene and a primary amine of theformula said catalyst giving in water at least the acidity of propicnicacid.

6. A process for preparing N-substituted pyrroles which comprisesreacting together under the influence of an acidic catalyst in liquidphase between 20 and C. l,4-bis(dimethylarnin0)-1,3-butadiene and aprimary amine of the formula said catalyst giving in water at least theacidity of propionic acid.

7. A process for preparing N-substituted pyrroles which comprisesreacting together under the influence of an acidic catalyst in liquidphase between 20 and 100 C. 1,4-bis(dimethylamino)-1,3-butadiene and aprimary amine of the formula said catalyst giving in water at least theacidity of propionic acid.

8. Pyrroles of the formula wherein A is an alkylene chain of two tothree carbon atoms.

9. The compound i on on o t ontornr \NH CHz'Ol g References Cited in thefile of this patent UNITED STATES PATENTS McKeever et a1. Nov. 11, 1952OTHER REFERENCES Eisleb: Chem. Abst., vol. 36, col. 5466 (1942).

1. A PROCESS FOR PREPARING N-SUBSTITUTED PYRROLES WHICH COMPRISESREACTING TOGETHER BETWEEN ABOUT 20* AND 150* C. IN LIQUID PHASE UNDERTHE INFLUENCE OF AN ACIDIC CATALYST GIVING IN WATER AT LEAST THE ACIDITYOF PROPIONIC ACID A PRIMARY AMINE HAVING AN IONIZATION CONSTANT OF ATLEAST 4.6X10-10 AND A BIS (TERT-AMINO)-1,3-BUTADIENE OF THE STRUCTURE 8.PYRROLES OF THE FORMULA